生物技术通报 ›› 2017, Vol. 33 ›› Issue (1): 48-57.doi: 10.13560/j.cnki.biotech.bull.1985.2017.01.005

• 特约综述 • 上一篇    下一篇

天然产物合成生物学体系的优化策略

匡雪君1, 邹丽秋1, 孙超1, 陈士林2   

  1. 1. 中国医学科学院北京协和医学院药用植物研究所,北京 100193;
    2. 中国中医科学院中药研究所,北京 100700
  • 收稿日期:2016-10-22 出版日期:2017-01-25 发布日期:2017-01-19
  • 作者简介:匡雪君,女,硕士研究生,研究方向:天然药物的代谢工程与合成生物学;E-mail:kuangxuejun@126.com
  • 基金资助:
    国家自然科学基金面上项目(81273485,81573704)

Optimization Strategies for Synthetic Biological Systems of Natural Products

KUANG Xue-jun1, ZOU Li-qiu1, SUN Chao1, CHEN Shi-lin2   

  1. 1. Institute of Medicinal Plant Development,China Academy of Medical Sciences and Peking Union Medical College,Beijing 100193;
    2. Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700
  • Received:2016-10-22 Published:2017-01-25 Online:2017-01-19

摘要: 天然产物是新药研发的重要源泉。天然产物合成生物学通过设计、重构目标化合物的高效生物合成途径,借助宿主改造,利用发酵生产目标化合物,可以有效弥补有机合成化学在复杂天然产物类药物生产方面的不足。虽然合成生物学已经取得了一些进展,但是通过合成生物学技术使目标产物的产量达到工业化生产水平依然是一项非常具有挑战性的任务。综述了天然产物合成生物学体系的优化策略,通过综合运用单个元件、外源代谢途径、底盘系统和发酵条件的优化技术,可以实现生物合成系统的最优化,最大化目标产物的产量,为来源稀缺的复杂天然产物的开发提供持续、稳定、经济的原料供给,推动天然产物类新药的研发。

关键词: 天然产物, 合成生物学, 优化, 底盘

Abstract: Natural products have become an important source of new drugs. However,there are some deficiencies while producing complex natural products by classical organic synthesis,one measure to efficiently make up those deficiencies is to apply synthetic biology in the biosynthesis of natural product,i.e.,designing and reconstructing efficient biosynthetic pathways of target compounds,re-engineering it in host cells,and producing target compounds by fermentation. However,achieving the yield of target product to the industrial level through technology of synthetic biology is still very challenging though there have been advances in synthetic biology. Here,we review various pathway optimization strategies for the synthetic biological systems of natural products. Via optimization technologies of fine-tuning individual component,exogenous metabolic pathways,the chassis systems,and fermentation conditions,the synthetic biological system may be optimized,and the yield of target product may be maximized,thus providing continuous,stable and economical raw material supplies for the manufacture of complex natural products while source is rare,and promoting the research and development of new drugs similar to natural products

Key words: natural products, synthetic biology, optimization, chassis